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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
When childhood leukaemia comes back, chemotherapy alone cures fewer than half. Three immune treatments changed this: blinatumomab, which links the child's T-cells to leukaemia cells and beat chemotherapy in two trials; tisagenlecleucel, the first approved CAR T-cell therapy, which put over eight in ten pretreated children into remission; and the antibody-drug conjugate inotuzumab ozogamicin.
Relapse is classified by time from diagnosis, site and response. Early relapse, within 18 months of diagnosis or within six months of finishing treatment, is much harder to cure than late relapse; isolated extramedullary relapse in the central nervous system or testis does better than marrow relapse; and residual disease after the first reinduction block sorts children into those who can be cured with chemotherapy alone and those who need transplant. T-cell ALL relapse carries the worst prognosis. The UK ALLR3 trial in 2010 showed that mitoxantrone in reinduction beat idarubicin, three-year progression-free survival 64.6 percent against 35.9 percent, and mitoxantrone-based reinduction with allogeneic transplant for high-risk relapse became the international standard.
Blinatumomab, a CD19 and CD3 bispecific T-cell engager, was tested against chemotherapy in two randomised trials of first relapse published together in 2021. In COG AALL1331, children with high- and intermediate-risk relapse given blinatumomab instead of two chemotherapy blocks before transplant had two-year disease-free survival of 54.4 percent against 39.0 percent and overall survival of 71.3 percent against 58.4 percent, with more reaching transplant in remission and fewer deaths from infection. In the European IntReALL trial, high-risk first relapse treated with one blinatumomab cycle instead of a third consolidation block had events in 31 percent against 57 percent and residual-disease remission in 90 percent against 54 percent. Tisagenlecleucel, an autologous CD19 CAR T-cell product, produced an overall remission rate of 81 percent within three months in 75 children and young adults with second or later relapse or refractory disease in ELIANA, with event-free survival of 50 percent and overall survival of 76 percent at twelve months; it was approved in August 2017, the first CAR T-cell therapy for any cancer, and long-term follow-up shows durable remissions in a substantial minority without transplant. Inotuzumab ozogamicin, a CD22 antibody-drug conjugate, gave complete remissions in most children in the ITCC-059 and COG AALL1621 studies and was approved for children from the age of one in March 2024.
| Setting | Approach | Guideline |
|---|---|---|
| First relapse: reinduction | Mitoxantrone-based reinduction (UKALLR3) with vincristine, dexamethasone, asparaginase and intrathecal therapy; MRD after the block sets the path. | not mapped |
| First relapse, high or intermediate risk: consolidation | Blinatumomab in place of chemotherapy blocks (AALL1331, IntReALL), then allogeneic transplant in MRD-negative remission. | not mapped |
| Second or later relapse, or refractory disease | Tisagenlecleucel (ELIANA) or inotuzumab ozogamicin, with transplant after inotuzumab and after CAR T-cells in selected children. | not mapped |
| Relapsed T-cell ALL | Nelarabine with cyclophosphamide and etoposide, then allogeneic transplant; venetoclax combinations and CD7 CAR T-cells in trials. | not mapped |
| Relapsed KMT2A-rearranged ALL | Revumenib (approved from the age of one) alone or in trials with chemotherapy, as a bridge to transplant. | not mapped |